NSUN2 p.Val58=
c.174G>A · rs745966593 · VCV436084
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.073 | GERP -2.1, phastCons 0.92 |
| Overall | ||
| CADD | 11.67 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,938 alleles
Filtering AF
0.000803%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00065%
Overall
0.00118%
19/1,614,086 alleles · very rare
exomes 16/1,461,888 · genomes 3/152,198 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,469 |
| Admixed American | 0.00167% | 60,010 |
| European (non-Finnish) | 0.00136% | 73,752 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- NSUN2
- Protein
- p.Val58=
- Coding
- c.174G>A
- MANE Select
- NM_017755
- dbSNP
- rs745966593
- Type
- single nucleotide variant
- Location
- chr5:6632679 (GRCh38)
- Gene constraint
- LOEUF 0.965 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.09 · 11 PDB
Similar variants
- NSUN2 p.Val58Met Uncertain significance ★ ⚠ same residue
- NSUN2 c.1601+1G>A Likely pathogenic ★★ same type
- NSUN2 c.360-1G>C Pathogenic/Likely pathogenic ★★ same type
- NSUN2 p.Arg264Ter Pathogenic/Likely pathogenic ★★ same type
- NSUN2 p.Arg389Ter Pathogenic/Likely pathogenic ★★ same type
- NSUN2 p.Arg408Ter Pathogenic/Likely pathogenic ★★ same type
- NSUN2 p.Ser139Ter Pathogenic ★★ same type
- NSUN2 p.Trp377Ter Pathogenic ★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/nsun2-p-val58 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown